An antihypertensive lactoferrin hydrolysate inhibits angiotensin I-converting enzyme, modifies expression of hypertension-related genes and enhances nitric oxide production in cultured human endothelial cells

Abstract

This study was aimed to explore whether an antihypertensive lactoferrin hydrolysate (LFH) can inhibit angiotensin I-converting enzyme (ACE) activity and modify the expression of genes related to hypertension in human umbilical vein endothelial cells (HUVEC). LFH induced significant inhibition of ACE activity but it did not affect ACE mRNA levels after 24 h of exposure. LFH treatment significantly affected the expression of genes encoding for proteins involved in nitric oxide pathway such as soluble guanylate cyclase 1 α3 subunit (GUCY1A3; 4.42-fold increase) and nitric oxide synthase trafficking (NOSTRIN; 2.45-fold decrease). Furthermore, expression of the PTGS2/COX-2 gene encoding prostaglandin-endoperoxide synthase 2 a key component of prostaglandin synthesis was significantly increased (2.23-fold). Moreover, NOSTRIN mRNA downregulation was consistent with reduced NOSTRIN protein expression and increased NO production observed in HUVEC. The present study reveals the complexity of the effects exerted by LFH opening avenues for the better understanding of its antihypertensive effects.